A Phase III Randomized Study of BBI608 and Best Supportive Care versus Placebo and Best Supportive Care in Patients with Pretreated Advanced Colorectal Carcinoma

INTERVENTION: Group 1: Best supportive care plus BBI608. Best supportive care defined as those measures designed to provide palliation of symptoms and improve quality of life as much as possible. BBI608 will be self‐administered by participants at 480mg (6 x 80mg tablets) orally twice daily (960mg total daily dose) in 28 day cycles. Patients may continue to receive protocol therapy as long as they have not experienced any adverse events requiring permanent discontinuation of study medication and are, in the opinion of the investigator, continuing to derive benefit from protocol therapy. Patients will be asked to keep a diary of when they take the capsules and if they miss any doses to monitor adherance. Patients will also be asked to return any tablets which were not taken. CONDITION: Advanced (metastatic or locally advanced) colorectal cancer PRIMARY OUTCOME: Overall survival (death from any cause) SECONDARY OUTCOME: Disease control rate (the proportion of patients with a documented complete response, partial response and stable disease (CR + PR + SD) based on RECIST 1.1 criteria) Quality of Life (using EORTC QLQ‐C30) Safety profile (adverse events graded according to NCI CTC AE Version 4.0) To evaluate progression free survival (disease progression or death) and objective response rate INCLUSION CRITERIA: 1. Signed, written informed consent 2. Must have histologically confirmed advanced (metastatic or locally advanced) colorectal cancer that is unresectable 3. Received a prior thymidylate synthase inhibitor (e.g. 5‐fluorouracil (5‐FU), capecitabine, raltitrexed, UFT) for metastatic disease or as adjuvant therapy. Thymidylate synthase inhibitor may have been given in combination with oxaliplatin or irinotecan 4. Received and failed an irinotecan ‐containing regimen (i.e. single‐agent or in combination) for treatment of metastatic disease, OR relapsed within 6 months of completion of an irinotecan‐containing adjuvant therapy, OR have documented unsuitability for an irinotecan‐containing regimen 5. Received and failed an oxaliplatin‐containing regimen (i.e. single‐agent or in combination) for treatment of metastatic disease, OR relapsed within 6 months of completion of an oxaliplatin‐containing adjuvant therapy OR have documented unsuitability for an oxa